- 2015Pump Priming
Bile acid metabolism and recycling in improving type 2 diabetes resolution after bariatric surgeryRecipient:Dr Jia LiInstitution:Imperial College LondonCity:LondonAmount:£19,672Description: Roux-en-Y gastric bypass (RYBG) surgery is effective in treating morbid obesity and it carries a so-called ‘magic effect’, such as remission of type 2 diabetes (T2D). Recently, increasing scientific evidence suggest that bile acids, a group of molecules regulating lipid metabolism and secretion of gut hormone and insulin, play an essential role in T2D remission. The aim of my study is to determine what types of bile acids are re-absorbed and how they link to T2D remission after RYGB. Gut contents, portal vein blood through which the re-absorbed bile acids come back to the liver and the liver will be collected from fatty and diabetic rats, either undergone RYGB surgery,sham operation or caloric restriction. Bile acid composition of all samples will be measured using mass spectrometry. These resulting findings will lead to discoveries of new treatment and direct us towards a safer and non-invasive way of treating diabetes.
- 2015Pump Priming
Does reorganisation of the Extracellular Matrix promote glucose induced fibrosis in Diabetic Nephropathy?Recipient:Dr Claire HillsInstitution:University of LincolnCity:LincolnAmount:£18,000Description: In the diabetic kidney, a build up of fibrotic material in the proximal region of the nephron, in part, mediates both structural and functional damage culminating in loss of both cell integrity and function. Damage occurs when cells fail to respond as they should, and thus start behaving more characteristic of cells of another tissue type. In doing so, cells lose their ability to synchronize their activity with neighbouring cells. They become less able to directly adhere to surrounding cells and to the extracellular matrix; a skeleton, which surrounds and supports the cell. Loss of these interactions results in failure of transmission of cell survival signals. To date we know little of how high levels of glucose disrupts, both cell structure and function in the proximal nephron. The current proposal will utilize healthy and diseased proximal tubule cells to establish how high glucose and downstream fibrotic Transforming Growth Factor Beta both regulate and disrupt cell-cell and cell-ECM interactions. The aim of these studies is to identify a future therapeutic target for alleviating renal fibrosis in diabetes.
- 2015Pump Priming
Investigation of anti-insulin receptor antibodies as a potential therapy for human insulin receptoropathy.Recipient:Dr Gemma BrierleyInstitution:University of CambridgeCity:CambridgeAmount:20,000Description: Insulin works by binding to a receptor protein on the surface of cells. Certain rare mutated forms of this receptor are normally inserted into the membrane that surrounds cells, but cannot be activated by insulin. In severe cases this causes growth retardation, severe, early diabetes and usually death in childhood, and to date there has been no way to bypass the blocking effect of such receptor mutations. Antibodies that bind and activate the insulin receptor in a different way to insulin may be able to activate mutant receptors for clinical benefit, however. This project will set out to test in cell models whether particular mutations can be identified which are likely to respond to this potential treatment by assessing the effect of the antibodies on the ability of the mutant receptors to bind insulin and send signals into cells that result in metabolically relevant biological outcomes.
- 2015Pump Priming
Is high intensity interval training an efficient and effective form of exercise for people with type 1 diabetes?Recipient:Dr Sam ShepherdInstitution:Liverpool John Moores UniversityCity:LiverpoolAmount:£19,811Description: Regular exercise reduces the risk of cardiovascular disease in people with T1D and increases life expectancy. However, few people with T1D perform enough exercise to observe health benefits, citing ‘lack of time’ and worry about hypoglycaemia as the primary reasons. HIT is an exercise mode that involves repeated bouts of short (30 sec) high intensity exercise interspersed with longer periods of rest/recovery (up to 4 minutes). It takes far less time than conventional exercise, with our previous research showing greater adherence and similar health improvements as normal exercise in non-diabetics. This project will investigate whether HIT when compared to moderate-intensity exercise: a) limits the risk of hypoglycaemia following exercise, since less energy is used during HIT than normal exercise with a smaller fall in blood glucose expected, and b) improves markers of health and well-being in people with T1D.
- 2015Sutherland-Earl Clinical Fellowship
Mechanisms and prognostication of type 2 diabetes resolution following bariatric surgeryRecipient:Mr Nicholas PenneyInstitution:Imperial College LondonCity:LondonAmount:£209,164Description: Bariatric (weight loss) surgery is currently the most successful treatment for obesity. Bariatric surgery has also emerged as a highly effective treatment of type 2 diabetes in obese patients, rapidly reducing and often removing the need for patients to take diabetic medications. Interestingly, the improvement in patients’ diabetes after bariatric surgery occurs long before any significant weight loss. Through a better understanding of the reasons behind this, bariatric surgery can provide a unique 'looking glass' to identify new, non-surgical ways of treating diabetes and obesity. Recent studies have shown that bacteria within the gut play an important role in the improvement seen in patients’ diabetes. Bariatric surgery fundamentally changes the environment within the gut, which results in changes to the makeup of the trillions of bacteria living within it. These changes in the gut bacteria can affect the body in a number of complex ways, which we are only just beginning to understand. For example, gut bacteria breakdown food we are unable to absorb ourselves, leading to altered sugar levels and can release molecules that act to increase insulin sensitivity or reduce appetite. In this study I aim to characterise the changes that occur to the gut bacteria after bariatric surgery and gain a better understanding of how these changes lead to an improvement in diabetes. With this understanding I hope to discover potential targets for future treatments, such as identifying beneficial gut bacteria that could be supplemented with probiotics in patients. Additionally, although bariatric surgery is a highly successful treatment, approximately 30% of obese patients do not undergo a significant improvement in their diabetes after surgery. I aim to identify molecules (metabolites) within the patient's blood or urine that are able to predict the likely chance a patient will undergo improvement in their diabetes after bariatric surgery. This will help doctors and patients assess the likely benefit from bariatric surgery, thus enabling a personalised approach towards patient care.